The clot consists of fibrin in which blood corpuscles are entangled.
It is clear that if any one of the reacting agents can be removed
or rendered inert the clotting cannot take place. There is only one
inorganic substance taking part in the reaction, and it is this
factor that is more easily removed than any of the others. Calcium
is precipitated in an insoluble form by various chemical reagents,
but it is obvious that for purposes of transfusion the formation
of an insoluble precipitate is not permissible. It is therefore
necessary to use a substance which will form a soluble compound with
the calcium and which is at the same time harmless when introduced
into the circulation. The only substance which has been found at
present to possess both these properties is citrate of sodium.
This forms with calcium a soluble double salt, in which calcium is
rendered inert. It is usually held that the calcium to be active
must be present in the ionized form, but recent investigations by
Vines into the rôle of calcium tend to modify slightly the accepted
view of its action. He has shown that calcium is present in the
blood in two forms, ionized and combined, and that both take part
in the coagulation reaction. He has, in addition, demonstrated that
a quantity of anticoagulant sufficient to combine with the whole of
the calcium present in a given quantity of blood is not enough to
prevent coagulation. It seems, therefore, that the anticoagulant acts
by combining with a large organic molecule of which calcium is only
one constituent, and not merely by combining with ionized calcium.
The organic complex with which the calcium is associated possibly
corresponds to the thrombokinase of the theory.
About the time that the use of the citrated blood was introduced
by Lewisohn, some investigations upon animals were carried out by
Salant and Wise in order to determine how sodium citrate was dealt
with and eliminated by the body. These observers found that it very
quickly disappeared from the circulation, nearly 90 per cent. of the
salt having been got rid of within ten minutes of its intravenous
injection. Part of the citrate is destroyed by oxidation, and the
rest, 30 to 40 per cent., is eliminated by the kidneys, the urine
being rendered alkaline. It was also shown that if a very large
dose was given, so large that toxic symptoms resulted, the effect
was rapidly obtained; but that if the toxic dose were not fatal,
no remote effects followed. Its injection never resulted in any
albuminuria.
Lewisohn showed by experiment on the human subject that up to 5
grammes of sodium citrate in the form of a 0·2 per cent. solution
could be injected intravenously without any harmful results. It
was also shown that this concentration of the salt was sufficient
to prevent clotting outside the body, and that the microscopic
appearance of the blood cells was not altered by the admixture of
this solution.
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